Macular degeneration is a disease of the retina which affects over thirteen million people in the United States and is characterized by loss of central vision due to the loss of photoreceptors in the central part of the retina, the macula lutea. D'Amico et al. (1994) New England J. Med. 331:95-106 and Kliffen et al. (1997) Microscopy Res. & Techniq. 36:106-122. The macula is the most important part of the eye for high resolution vision because there is a greater concentration of cone type photoreceptors which are responsible for color vision and visual acuity.
Photoreceptor cells, especially rod cells, renew their outer segments at a high rate. Thus, as new lamellae discs are formed and added to the photoreceptor cells, the older lamellae discs at the tip are discarded. Retinal pigment epithelial (RPE) cells function to provide support for the retinal photoreceptors and are responsible for the metabolic digestion of the discarded outer segments of the neural retina. Thus, RPE cells are responsible for the phagocytosis and digestion of the discarded discs at a turn over rate of approximately 30-100 discs each day. Underlying the RPE cells is the choriocapillaris which contains the vasculature to provide nutrients and remove metabolic by-products from the retina.
In macular degeneration, the RPE cells are dysfunctional, thereby leading to a build up of metabolic by-products, including discarded discs in the retina. The presence of metabolic debris and excess fluid in the retina damage photoreceptor cells, thereby compromising visual acuity. Cingle et al. (1996) Curr. Eye. Res. 15:433-438 and Curcio et al. (1996) Invest. Ophthal. & Vis. Sci. 37:1236-1249. In addition, the degeneration of the RPE layer is also reflected by ensuing atrophy of the choriocapillaris.
In the dry form of macular degeneration, loss of vision is gradual and is associated with retinal pigment changes, deposits in the subretinal space called drusen, atrophy of the blood vessels supplying the retina and ultimately geographic atrophy in the absence of neovascularization. Although this form of macular degeneration has a slower progression to blindness, it is far more common, accounting for approximately 90% of the cases of acute macular degeneration. In the wet form of the disease, vessels arise from the choriocapillaris and penetrate Bruch's membrane and the RPE cell layer to impinge upon the neural retina where they cause damage that leads to loss of central vision. Patients with the wet form of the disease are at high risk for subretinal neovascularization, geographic atrophy and retinal pigment epithelial detachment, all of which result in a rapid and severe loss of visional acuity.
Currently, there are few therapeutic alternatives for patients diagnosed with macular degeneration. Laser photocoagulation has been used for some cases of the wet form of the disease, but the clinical experience with this therapy has not been promising. If the retinal damage is close to the fovea, laser therapy is withheld to avoid potential loss of central photoreceptors. Lambert et al. (1992) Am. J. Ophthalmol. 113:257-262. In addition, radiation and photodynamic therapy has been performed for cases where neovascularization is diffuse or too severe. Although follow-up data showed an advantage of laser photocoagulation, reoccurrence of neovascularization occurred in over half of the patients, thereby undermining the initial benefit of the treatment. Macular Photocoagulation Study Group (1993) Arch. Ophthalmol. 111:1200-1209.
Opthalmic surgery can also be performed to remove neovascularization in the wet form of macular degeneration. Although this surgery has been reported to reduce the progression of the disease, restoration of visual acuity is limited.
The other competitive approach to treating macular degeneration is surgical implantation of human RPE cells. Although early clinical analysis has been promising, broader clinical application of human transplants to patients with macular degeneration will be extremely limited by the availability of human donors. Thus, a need exists for alternative sources of retinal cells and methods of retinal transplantation which can minimize the damage caused by retinal disorders such as macular degeneration.